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The prevalence of type 2 diabetes mellitus (T2DM) is alarming because it is always linked to the increase in chronic diseases, mortality, and socioeconomic burden. Water kefir has a wide range of functional and probiotic characteristics attributed to the microorganisms present in the kefir grains. The present study aims to evaluate the in vivo anti-diabetic potential of the isolated Lactobacillus paracasei from Malaysian water kefir grains (MWKG) which was reported to have excellent probiotic properties and high antioxidant activities as reported previously. High-fat diet/streptozotocin (HFD/STZ) induction was used to obtain a T2DM model followed by treatment with the isolated L. paracasei from MWKG. The levels of glucose, insulin, and in vivo liver antioxidants were quantified after 14 weeks. Gene expression analysis of the liver was also carried out using microarray analysis, and several genes were selected for validation using quantitative real-time PCR. Insulin tolerance test demonstrated that the L. paracasei isolated from the MWKG alleviated T2DM by improving the area under the curve of the insulin tolerance test whereby low-dose and high-dose concentrations treated groups showed 2424.50 ± 437.02 mmol/L·min and 2017.50 ± 347.09 mmol/L·min, respectively, compared to untreated diabetic mice which was 3884.50 ± 39.36 mmol/L·min. Additionally, treatment with the isolated L. paracasei from MWKG regulated the expression of several genes related to glucose homeostasis and lipid metabolism in diabetic mice. These results suggested that the isolated L. paracasei from MWKG could be a potential dietary supplement for T2DM., Competing Interests: Declarations Ethical Approval The in vivo study was performed according to the OECD guidelines with the approval of the Universiti Putra Malaysia Animal Care and Use Committee (UPM/IACUC/AUP-R025/2018). Competing Interests The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 2 diabetes (T2DM) is one of the four major types of non-communicable diseases that have become a global health concern. Water kefir is a product of a brown sugar solution fermented with kefir grains which comprises around 30 microbial species in its grains. Water kefir possesses a wide range of health benefits, including anti-hyperlipidemic effects, and reduces hypertension and blood glucose levels in animal models. Reportedly, consuming water kefir containing probiotics may enhance the intestinal barrier and positively influence the composition of the intestinal microflora. The present study aimed to evaluate the regulatory effects of Lactobacillus paracasei isolated from Malaysian water kefir grains (MWKG) on the alterations of intestinal barrier and gut microbiota in diabetic mice via histopathological analysis of the distal colon and 16S rRNA gene sequencing on fecal microbiome. Results indicated that the administration of isolated Lactobacillus paracasei from MWKG to diabetic mice ameliorated the dominant probiotic phyla in the gut microbiota. Results showed that lower dose (LD) and high dose (HD) treatments of the isolated Lactobacillus paracasei could significantly reduce inflammatory cell infiltration in the distal colon of diabetic mice. The treatments revealed a significant decrease in the relative abundance of Firmicutes in the gut, 0.27 ± 0.06% for LD and 0.34 ± 0.04% for HD, compared to untreated (UN) diabetic mice, 0.40 ± 0.02%. These results suggest that L. paracasei isolated from MWKG could serve as a potential dietary supplement against intestinal inflammation and modify gut microbiota composition in patients with T2DM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glioblastoma multiforme (GBM) is the most prevalent form of brain tumor, which generally has a poor prognosis. According to consensus, recurrence of the tumor and chemotherapy resistance acquisition are the two distinguishing features of GBM originated from glioblastoma stem cells (GSCs). To eliminate these obstacles inherent in GBM chemotherapy, targeting GSCs through a smart drug delivery system has come to the front position of GBM therapeutics. In this study, B19 aptamer (Apt)-conjugated polyamidoamine (PAMAM) G4C12 dendrimer nanoparticles (NPs), called Apt-NPs, were formulated for the co-delivery of paclitaxel (PTX) and temozolomide (TMZ) to U-87 stem cells. These drugs were loaded using a double emulsification solvent evaporation method. As a result, drug-loaded Apt-NPs significantly inhibited the tumor growth of U-87 stem cells, by the initiation of apoptosis via the downregulation of autophagic and multidrug resistance (MDR) genes. Additionally, by their downregulation by qPCR of CD133, CD44, SOX2, and the canonical Wnt/β-catenin pathway, cell proliferation has substantially decreased. Altogether, the results demonstrate that this intelligent drug co-delivery system is capable of effectively transferring PTX and TMZ to U-87 stem cells and without any toxic effect on Apt-NPs alone to U-87 stem cells. Furthermore, the designed dendrimer-based pharmaceutical system along with single-stranded B19 aptamer might be utilized as a new therapeutic strategy for the treatment of U-87 stem cells drug resistance in the GBM., (© 2021. Controlled Release Society.)

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.